SPECT neuroimaging and neuropsychological functions in different stages of Parkinson’s disease

  • Anna Paschali
  • Lambros Messinis
  • Odysseas Kargiotis
  • Velissarios Lakiotis
  • Zinovia Kefalopoulou
  • Costantinos Constantoyannis
  • Panagiotis Papathanasopoulos
  • Pavlos Vassilakos
Original Article



The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD).


We recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system and 20 healthy controls who were used in the comparison of the neuropsychological findings. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding) as well as neuropsychological evaluation. Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Mean values obtained from the cortical areas and neuropsychological measures in the different groups were also compared by analysis of covariance (ANCOVA) controlling for disease duration and educational level.


We found cognitive deficits especially in the late PD stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations between cognitive decrements and cortical perfusion deterioration mainly in the frontal and posterior cortical areas. Compared with controls, PD patients showed impairments of cognition and cerebral perfusion that increased with clinical severity. Furthermore, we found a significant correlation between the performance on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left frontal lobe. Dopamine transporter binding in the left caudate nucleus significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC), but not with measures of executive functions.


There are significant cognitive and perfusion deficits associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc).


Parkinson’s disease Brain perfusion SPECT Dopamine transporter SPECT Cognitive functions 


  1. 1.
    Dubois B, Pillon B. Cognitive deficits in Parkinson’s disease. J Neurol 1997;244:2–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Caviness JN, Driver-Dunckley E, Connor DJ, Sabbagh MN, Hentz JG, Noble B, et al. Defining mild cognitive impairment in Parkinson’s disease. Mov Disord 2007;22:1272–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Janvin CC, Larsen JP, Aarsland D, Hugdahl K. Subtypes of mild cognitive impairment in Parkinson’s disease: progression to dementia. Mov Disord 2006;21:1343–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Levin BE, Tomer R, Rey GJ. Cognitive impairments in Parkinson’s disease. Neurol Clin 1992;10:471–85.PubMedGoogle Scholar
  5. 5.
    Miller WC, DeLong MR. Parkinsonian symptomatology. An anatomical and physiological analysis. Ann N Y Acad Sci 1988;515:287–302.CrossRefPubMedGoogle Scholar
  6. 6.
    Cummings JL. Behavioral and psychiatric symptoms associated with Huntington’s disease. Adv Neurol 1995;65:179–86.PubMedGoogle Scholar
  7. 7.
    Litvan I, Paulsen JS, Mega MS, Cummings JL. Neuropsychiatric assessment of patients with hyperkinetic and hypokinetic movement disorders. Arch Neurol 1998;55:1313–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Mandir AS, Vaughan C. Pathophysiology of Parkinson’s disease. Int Rev Psychiatry 2000;12:270–80.CrossRefGoogle Scholar
  9. 9.
    Derejko M, Slawek J, Wieczorek D, Brochhuis B, Dubaniewicz M, Lass P. Regional cerebral blood flow in Parkinson’s disease as an indicator of cognitive impairment. Nucl Med Commun 2006;27:945–51.CrossRefPubMedGoogle Scholar
  10. 10.
    Liu RS, Lin KN, Wang SJ, Shan DE, Fuh JL, Yeh SH, et al. Cognition and 99Tcm-HMPAO SPECT in Parkinson’s disease. Nucl Med Commun 1992;13:744–8.PubMedGoogle Scholar
  11. 11.
    Matsui H, Udaka F, Miyoshi T, Hara N, Tamura A, Oda M, et al. N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography study of Parkinson’s disease with dementia. Intern Med 2005;44:1046–50.CrossRefPubMedGoogle Scholar
  12. 12.
    Spampinato U, Habert MO, Mas JL, Bourdel MC, Ziegler M, de Recondo J, et al. (99mTc)-HM-PAO SPECT and cognitive impairment in Parkinson’s disease: a comparison with dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry 1991;54:787–92.CrossRefPubMedGoogle Scholar
  13. 13.
    Sawada H, Udaka F, Kameyama M, Seriu N, Nishinaka K, Shindou K, et al. SPECT findings in Parkinson’s disease associated with dementia. J Neurol Neurosurg Psychiatry 1992;55:960–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Wallin A, Ekberg S, Lind K, Milos V, Granérus AK, Granerus G. Posterior cortical brain dysfunction in cognitively impaired patients with Parkinson’s disease—a rCBF scintigraphy study. Acta Neurol Scand 2007;116:347–54.CrossRefPubMedGoogle Scholar
  15. 15.
    Antonini A, De Notaris R, Benti R, De Gaspari D, Pezzoli G. Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson’s disease. Neurol Sci 2001;22:45–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Firbank MJ, Molloy S, McKeith IG, Burn DJ, O’Brien JT. Longitudinal change in 99mTcHMPAO cerebral perfusion SPECT in Parkinson’s disease over one year. J Neurol Neurosurg Psychiatry 2005;76:1448–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Paschali A, Messinis L, Lyros E, Constantoyannis C, Kefalopoulou Z, Lakiotis V, et al. Neuropsychological functions and rCBF SPECT in Parkinson’s disease patients considered candidates for deep brain stimulation. Eur J Nucl Med Mol Imaging 2009;36:1851–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Fahn S, Elton RL, Members of the UPDRS Development Committee, et al. Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, et al., editors. Recent developments in Parkinson’s disease, Vol II. New Jersey: Macmillan Healthcare Information; 1987. p. 153–63.Google Scholar
  19. 19.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Text Revision. 4th ed. Washington, DC: American Psychiatric Association; 2000.CrossRefGoogle Scholar
  20. 20.
    Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98.CrossRefPubMedGoogle Scholar
  21. 21.
    Berg L. Clinical Dementia Rating (CDR). Psychopharmacol Bull 1988;24:637–9.PubMedGoogle Scholar
  22. 22.
    Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–86.PubMedGoogle Scholar
  23. 23.
    Steer RA, Ranieri WF, Kumar G, Beck AT. Beck Depression Inventory-II items associated with self-reported symptoms of ADHD in adult psychiatric outpatients. J Pers Assess 2003;80:58–63.CrossRefPubMedGoogle Scholar
  24. 24.
    Messinis L, Tsakona I, Malefaki S, Papathanasopoulos P. Normative data and discriminant validity of Rey’s Verbal Learning Test for the Greek adult population. Arch Clin Neuropsychol 2007;22:739–52.CrossRefPubMedGoogle Scholar
  25. 25.
    Messinis L. Stroop neuropsychological screening test & repeatable battery for the assessment of neuropsychological status (RBANS) (translation and adaptation). In: Stalikas A, Triliva S, Roussi P, editors. Psychometric tools in Greece, 2nd ed. Ellinika Grammata; (in press).Google Scholar
  26. 26.
    Kosmidis MH, Vlahou CH, Panagiotaki P, Kiosseoglou G. The verbal fluency task in the Greek population: normative data, and clustering and switching strategies. J Int Neuropsychol Soc 2004;10:164–72.PubMedGoogle Scholar
  27. 27.
    Chang LT. A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978;25:638–43.CrossRefGoogle Scholar
  28. 28.
    Ferrer I. Early involvement of the cerebral cortex in Parkinson’s disease: convergence of multiple metabolic defects. Prog Neurobiol 2009;88:89–103.CrossRefPubMedGoogle Scholar
  29. 29.
    Rashkin SA, Borod JC, Tweedy J. Neuropsychological aspects of Parkinson’s disease. Neuropsychol Rev 1990;1:185–219.CrossRefGoogle Scholar
  30. 30.
    Takeda A, Mallory M, Sundsmo M, Honer W, Hansen L, Masliah E. Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. Am J Pathol 1998;152:367–72.PubMedGoogle Scholar
  31. 31.
    Burke RE, Dauer WT, Vonsattel JPG. A critical evaluation of the Braak staging scheme for Parkinson’s disease. Ann Neurol 2008;64:485–91.CrossRefPubMedGoogle Scholar
  32. 32.
    Kandiah N, Narasimhalu K, Lau PN, Seah SH, Au WL, Tan LC. Cognitive decline in early Parkinson’s disease. Mov Disord 2009;24:605–16.CrossRefPubMedGoogle Scholar
  33. 33.
    Koerts J, Leenders KL, Brouwer WH. Cognitive dysfunction in non-demented Parkinson’s disease patients: controlled and automatic behavior. Cortex 2009;45:922–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Martin GN. Human neuropsychology, 2nd ed. Pearson education; 2006.Google Scholar
  35. 35.
    Forno LS. Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 1996;55:259–72.CrossRefPubMedGoogle Scholar
  36. 36.
    Cash R, Dennis T, L’Heureux R, Raisman R, Javoy-Agid F, Scatton B. Parkinson’s disease and dementia: norepinephrine and dopamine in locus ceruleus. Neurology 1987;37:42–6.PubMedGoogle Scholar
  37. 37.
    Whitehouse PJ, Hedreen JC, White CL 3rd, Price DL. Basal forebrain neurons in the dementia of Parkinson disease. Ann Neurol 1983;13:243–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Owen AM, Doyon J, Dagher A, Sadikot A, Evans AC. Abnormal basal ganglia outflow in Parkinson’s disease identified with PET. Implications for higher cortical functions. Brain 1998;121:949–65.CrossRefPubMedGoogle Scholar
  39. 39.
    Hosokai Y, Nishio Y, Hirayama K, Takeda A, Ishioka T, Sawada Y, et al. Distinct patterns of regional cerebral glucose metabolism in Parkinson’s disease with and without mild cognitive impairment. Mov Disord 2009;24:854–62.CrossRefPubMedGoogle Scholar
  40. 40.
    Kikuchi A, Takeda A, Kimpara T, Nakagawa M, Kawashima R, Sugiura M, et al. Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson’s disease. J Neurol Sci 2001;193:29–36.CrossRefPubMedGoogle Scholar
  41. 41.
    Imon Y, Matsuda H, Ogawa M, Kogure D, Sunohara N. SPECT image analysis using statistical parametric mapping in patients with Parkinson’s disease. J Nucl Med 1999;40:1583–9.PubMedGoogle Scholar
  42. 42.
    Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, et al. Changes in network activity with the progression of Parkinson’s disease. Brain 2007;130:1834–46.CrossRefPubMedGoogle Scholar
  43. 43.
    Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986;9:357–81.CrossRefPubMedGoogle Scholar
  44. 44.
    Lehéricy S, Ducros M, Van de Moortele PF, Francois C, Thivard L, Poupon C, et al. Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Ann Neurol 2004;55:522–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Postuma RB, Dagher A. Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications. Cereb Cortex 2006;16:1508–21.CrossRefPubMedGoogle Scholar
  46. 46.
    Müller U, Wächter Τ, Barthel Η, Reuter Μ, von Cramon DY. Striatal [123I]beta-CIT SPECT and prefrontal cognitive functions in Parkinson’s disease. J Neural Transm 2000;107:303–19.CrossRefPubMedGoogle Scholar
  47. 47.
    Mozley LH, Gur RC, Mozley PD, Gur RE. Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry 2001;158:1492–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Marié RM, Barré L, Dupuy B, Viader F, Defer G, Baron JC. Relationships between striatal dopamine denervation and frontal executive tests in Parkinson’s disease. Neurosci Lett 1999;260:77–80.CrossRefPubMedGoogle Scholar
  49. 49.
    Rinne JO, Portin R, Ruottinen H, Nurmi E, Bergman J, Haaparanta M, et al. Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study. Arch Neurol 2000;57:470–5.CrossRefPubMedGoogle Scholar
  50. 50.
    Innis RB, Marek KL, Sheff K, Zoghbi S, Castronuovo J, Feigin A, et al. Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]beta-CIT. Mov Disord 1999;14:436–44.CrossRefPubMedGoogle Scholar
  51. 51.
    Melamed E, Lavy S, Cooper G, Bentin S. Regional cerebral blood flow in parkinsonism. Measurement before and after levodopa. J Neurol Sci 1978;38:391–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Kobari M, Fukuuchi Y, Shinohara T, Obara K, Nogawa S. Levodopa-induced local cerebral blood flow changes in Parkinson’s disease and related disorders. J Neurol Sci 1995;128:212–8.CrossRefPubMedGoogle Scholar
  53. 53.
    Gotham AM, Brown RG, Marsden CD. ‘Frontal’ cognitive function in patients with Parkinson’s disease ‘on’ and ‘off’ levodopa. Brain 1988;111:299–321.CrossRefPubMedGoogle Scholar
  54. 54.
    Mohr E, Fabbrini G, Ruggieri S, Fedio P, Chase TN. Cognitive concomitants of dopamine system stimulation in parkinsonian patients. J Neurol Neurosurg Psychiatry 1987;50:1192–6.CrossRefPubMedGoogle Scholar
  55. 55.
    Lange KW, Robbins TW, Marsden CD, James M, Owen AM, Paul GM. L-dopa withdrawal in Parkinson’s disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. Psychopharmacology (Berl) 1992;107:394–404.CrossRefGoogle Scholar
  56. 56.
    Müller T, Benz S, Börnke C. Delay of simple reaction time after levodopa intake. Clin Neurophysiol 2001;112:2133–37.CrossRefPubMedGoogle Scholar
  57. 57.
    Cooper JA, Sagar HJ, Doherty SM, Jordan N, Tidswell P, Sullivan EV. Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson’s disease. A follow-up study of untreated patients. Brain 1992;115:1701–25.CrossRefPubMedGoogle Scholar
  58. 58.
    Pillon B, Dubois B, Bonnet AM, Esteguy M, Guimaraes J, Vigouret JM, et al. Cognitive slowing in Parkinson’s disease fails to respond to levodopa treatment: the 15-objects test. Neurology 1989;39:762–8.PubMedGoogle Scholar
  59. 59.
    Darcourt J, Koulibaly PM, Migneco O. Exploring the central nervous system: methodological state of the art. Alasbimn J 2005;8:30–1.Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Anna Paschali
    • 1
  • Lambros Messinis
    • 2
  • Odysseas Kargiotis
    • 2
  • Velissarios Lakiotis
    • 1
  • Zinovia Kefalopoulou
    • 3
  • Costantinos Constantoyannis
    • 3
  • Panagiotis Papathanasopoulos
    • 2
  • Pavlos Vassilakos
    • 1
  1. 1.Department of Nuclear MedicineUniversity of Patras Medical SchoolPatrasGreece
  2. 2.Department of Neurology, Neuropsychology SectionUniversity of Patras Medical SchoolPatrasGreece
  3. 3.Department of NeurosurgeryUniversity of Patras Medical SchoolPatrasGreece

Personalised recommendations